Triethylamine → n-{(3r)-1-[4-Hydroxy-4-(2-isopropyl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl}-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamide

HRID 1809920Notes

Reaction equation

HRID 1809920 reaction equation
Cl.Cl.Cl.[NH2:4][C@@H:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][C:13]([C:17]3[S:21][C:20]([CH:22]([CH3:24])[CH3:23])=[N:19][CH:18]=3)([OH:16])[CH2:12][CH2:11]2)[CH2:6]1.[O:25]=[C:26]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=1)[CH2:27][CH2:28][C:29](O)=[O:30].CCN(CC)CC.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.CCOC(C)=O>[OH:16][C:13]1([C:17]2[S:21][C:20]([CH:22]([CH3:24])[CH3:23])=[N:19][CH:18]=2)[CH2:12][CH2:11][CH:10]([N:7]2[CH2:8][CH2:9][C@@H:5]([NH:4][C:29](=[O:30])[CH2:28][CH2:27][C:26](=[O:25])[C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:39])[F:40])[CH:33]=3)[CH2:6]2)[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 134088364-Oxo-4-(3-trifluoromethylphenyl)butyric acidHCID 667872284-[(3R)-3-aminopyrrolidin-1-yl]-1-(2-isopropyl-1,3-thiazol-5-yl)cyclohexanol 3HCl salt

Product 1

HCID 58751615n-{(3r)-1-[4-Hydroxy-4-(2-isopropyl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl}-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamideYield 25%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-[(3R)-3-aminopyrrolidin-1-yl]-1-(2-isopropyl-1,3-thiazol-5-yl)cyclohexanol 3HCl salt (0.233 g, 0.557 mmol) and 4-oxo-4-[3-(trifluoromethyl)phenyl]butanoic acid (0.15 g, 0.61 mmol) in DMF (5 mL) was added Et3N (0.34 mL, 2.44 mmol) followed by BOP (0.296 g, 0.67 mmol). The mixture was stirred overnight at room temperature. Then the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3 and brine. The organic layer was dried (MgSO4), concentrated and flash chromatographed (EtOAc to 10% MeOH/EtOAc) to give 0.075 g of the title compound. MS (EI) calculated: MS (EI) calcd: (M+H)+=538.2. Found: 538.1.

Workup

  1. washwashed with saturated Na2CO3 and brine
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated
  4. customflash chromatographed (EtOAc to 10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-6b25fb9f06f344acb63dce88c6dca75c
Source dataset
uspto-grants-2013_01
Patent number
US08362003B2

Reaction notes

Loading…